The role of nuclear receptor PXR in detoxification and clearance of xenobiotics and endobiotics is well-established. However, its projected role in hepatic cancer is rather illusive where its expression is reported altered in different cancers depending on the tissue-type and microenvironment. The expression of PXR, its target genes and their biological or clinical significance have not been examined in hepatic cancer. In the present study, by generating DEN-induced hepatic cancer in mice, we report that the expression of PXR and its target genes CYP3A11 and GSTa2 are down-regulated implying impairment of hepatic detoxification capacity. A higher state of inflammation was observed in liver cancer tissues as evident from upregulation of inflammatory cytokines IL-6 and TNF-α along with NF-κB and STAT3. Our data in mouse model suggested a negative correlation between down-regulation of PXR and its target genes with that of higher expression of inflammatory proteins (like IL-6, TNF-α, NF-κB). In conjunction, our findings with relevant cell culture based assays showed that higher expression of PXR is involved in reduction of tumorigenic potential in hepatic cancer. Overall, the findings suggest that inflammation influences the expression of hepatic proteins important in drug metabolism while higher PXR level reduces tumorigenic potential in hepatic cancer.

Proteomics continues to forge significant strides in the discovery of essential biological processes, uncovering valuable information on the identity, global protein abundance, protein modifications, proteoform levels, and signal transduction pathways. Cancer is a complicated and heterogeneous disease, and the onset and progression involve multiple dysregulated proteoforms and their downstream signaling pathways. These are modulated by various factors such as molecular, genetic, tissue, cellular, ethnic/racial, socioeconomic status, environmental, and demographic differences that vary with time. The knowledge of cancer has improved the treatment and clinical management; however, the survival rates have not increased significantly, and cancer remains a major cause of mortality. Oncoproteomics studies help to develop and validate proteomics technologies for routine application in clinical laboratories for (1) diagnostic and prognostic categorization of cancer, (2) real-time monitoring of treatment, (3) assessing drug efficacy and toxicity, (4) therapeutic modulations based on the changes with prognosis and drug resistance, and (5) personalized medication. Investigation of tumor-specific proteomic profiles in conjunction with healthy controls provides crucial information in mechanistic studies on tumorigenesis, metastasis, and drug resistance. This review provides an overview of proteomics technologies that assist the discovery of novel drug targets, biomarkers for early detection, surveillance, prognosis, drug monitoring, and tailoring therapy to the cancer patient. The information gained from such technologies has drastically improved cancer research. We further provide exemplars from recent oncoproteomics applications in the discovery of biomarkers in various cancers, drug discovery, and clinical treatment. Overall, the future of oncoproteomics holds enormous potential for translating technologies from the bench to the bedside.

Background: Amylin is a systemic hormone that is co‐secreted with insulin from pancreatic β‐cells. Amylin co‐aggregates with brain parenchymal and vascular β‐amyloid in persons with Alzheimer’s dementia. The present pilot study sought to assess the safety and side effects during and after the treatment period of passive amylin immunotherapy in the APP/PS1 mouse model of Alzheimer’s disease.Method: We have generated a polyclonal anti‐amylin antibody (P2) in rabbits using the N‐terminal of amylin peptide as an immunogen. In this pilot study at 5 months of age, male APP/PS1 mice were randomly assigned into rabbit Ig‐G vehicle‐control and P2 amylin antibody injected group (n = 4/group). Anti‐amylin antibody was injected at a dose of 10 mg/kg of body weight three times a week for six weeks. During the six weeks of amylin immunotherapy, we monitored the mice for visible side effects and immunocomplex disease‐related visible symptoms. Six weeks later, we assessed body weight, blood glucose level, and brain function with the novel object recognition test and performed comparative immunochemical Aβ analyses of hippocampal tissue by using MSD ELISA.Result: During the period of passive amylin immunotherapy, we did not observe visible symptoms of immunocomplex disease such as rash, urticaria, and malaise along with any sudden drop in body weight. Mice with anti‐amylin antibody injected showed an enhanced trend of recognition memory index (p = 0.1121) along with a lower blood glucose level (p = 0.2602) as compared to those that were injected with rabbit Ig‐G vehicle control. This was associated with decreasing trend of hippocampal levels of Aβ42 (p = 0.7872), Aβ40 (p = 0.4609), Aβ38 (p = 0.4473) in brain sup fraction, and Aβ42 levels (p = 0.6336) in brain pellet fraction measured by MSD ELISA.Conclusion: Passive amylin immunotherapy in APP/PS1 mice shows that used immunotherapy procedure might be safe for further investigation. Future experiments will be performed in APP/PS1 mouse model in which the mouse amylin gene is replaced by the human amylin gene in the pancreas and is conditionally downregulated by tamoxifen (TMX) injection, intraperitoneally.